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© The Rockefeller University Press, 0021-9525/2002/9/1152-a $5.00
The Journal of Cell Biology, Volume 158, Number 7, September 30, 2002 1152-a-1153

Signaling clusters caught in the act

Signaling complexes assemble soon after TCR ligation.

Biochemical studies have provided a detailed accounting of the molecules present in the T cell receptor (TCR) complex during T cell activation, but relatively little is known about the maturation and dynamic composition of these complexes. Now Bunnell et al., reporting on page 1263, have developed a novel assay that allows them to visualize the formation of these complexes in live cells.

The authors dropped live Jurkat leukemic T cells onto coverslips coated with anti-TCR antibodies, and then tracked chimeric signaling proteins as they associated with and dissociated from signaling complexes. TCR-signaling complexes develop within 15 s, and undergo dynamic assembly and disassembly throughout the process of contact formation. Initial clustering of the TCRs does not require phosphotyrosine-dependent interactions, but the formation of a functional signaling complex does. A lipid raft marker does not localize to the complexes, a result that should fan the controversy surrounding raft function in signaling.Molecules that are recruited to the complexes depart by distinct mechanisms. The adaptor protein SLP-76 exhibits a particularly striking pattern, departing TCR-rich signaling complexes in large structures that are transported along microtubules to accumulate in a novel perinuclear structure. Bunnell et al. suggest that signaling complexes are functioning as sorting structures, as molecules are recruited to the complexes from different compartments, then sent from the complexes in different ways.

Intracellular calcium elevations in the T cells begin within 12 s of contact initiation, suggesting that a single TCR cluster may be sufficient to produce calcium elevation. TCR clusters may therefore constitute "proto-synapses" capable of directing T cell activation, a model that may explain how some types of T cells are activated without the formation of well-defined immune synapses. The authors are now extending their assay to include more markers to characterize the process of complex formation in greater detail.

Alan W. Dove

alanwdove{at}earthlink.net

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T cell receptor ligation induces the formation of dynamically regulated signaling assemblies

Stephen C. Bunnell, David I. Hong, Julia R. Kardon, Tetsuo Yamazaki, C. Jane McGlade, Valarie A. Barr, and Lawrence E. Samelson
J. Cell Biol. 2002 158: 1263-1275. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 294K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?